Identification of a quality-control factor that monitors failures during proteasome assembly

doi:10.1126/science.abc6500

GSTDTAP > 气候变化

DOI	10.1126/science.abc6500
	Identification of a quality-control factor that monitors failures during proteasome assembly
	Eszter Zavodszky; Sew-Yeu Peak-Chew; Szymon Juszkiewicz; Ana J. Narvaez; Ramanujan S. Hegde
	2021-08-27
发表期刊	Science
出版年	2021
英文摘要	The assembly of multiprotein complexes inside the cell requires each subunit to be produced at a defined level relative to its partners. Imbalances in subunit synthesis are inevitable, necessitating the elimination of unassembled intermediates. Zavodszky et al. found that a ubiquitin ligase called HERC1 is responsible for marking certain assembly intermediates of the proteasome for degradation. HERC1 finds these intermediates by recognizing a proteasome assembly factor that normally dissociates when assembly is complete. A point mutation in HERC1 that impairs its ability to recognize proteasome assembly intermediates causes neurodegeneration in mice, highlighting the importance of this quality control pathway. Science , abc6500, this issue p. [998][1] In eukaryotic cells, half of all proteins function as subunits within multiprotein complexes. Imbalanced synthesis of subunits leads to unassembled intermediates that must be degraded to minimize cellular toxicity. Here, we found that excess PSMC5, a subunit of the proteasome base, was targeted for degradation by the HERC1 ubiquitin ligase in mammalian cells. HERC1 identified unassembled PSMC5 by its cognate assembly chaperone PAAF1. Because PAAF1 only dissociates after assembly, HERC1 could also engage later assembly intermediates such as the PSMC4-PSMC5-PAAF1 complex. A missense mutant of HERC1 that causes neurodegeneration in mice was impaired in the recognition and ubiquitination of the PSMC5-PAAF1 complex. Thus, proteasome assembly factors can serve as adaptors for ubiquitin ligases to facilitate elimination of unassembled intermediates and maintain protein homeostasis. [1]: /lookup/doi/10.1126/science.abc6500
领域	气候变化 ; 资源环境
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文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/336660
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Eszter Zavodszky,Sew-Yeu Peak-Chew,Szymon Juszkiewicz,et al. Identification of a quality-control factor that monitors failures during proteasome assembly[J]. Science,2021.
APA	Eszter Zavodszky,Sew-Yeu Peak-Chew,Szymon Juszkiewicz,Ana J. Narvaez,&Ramanujan S. Hegde.(2021).Identification of a quality-control factor that monitors failures during proteasome assembly.Science.
MLA	Eszter Zavodszky,et al."Identification of a quality-control factor that monitors failures during proteasome assembly".Science (2021).